The therapeutic value of protein (de)nitrosylation in experimental septic shock.

Cardiovascular dysfunction and organ damage are hallmarks of sepsis and septic shock. Protein S-nitrosylation by nitric oxide has been described as an important modifier of protein function. We studied whether protein nitrosylation/denitrosylation would impact positively in hemodynamic parameters of septic rats. Polymicrobial sepsis was induced by cecal ligation and puncture. Female Wistar rats were treated with increasing doses of DTNB [5,5'-dithio-bis-(2-nitrobenzoic acid)] 30min before or 4 or 12h after sepsis induction. Twenty-four hours after surgery the following data was obtained: aorta response to phenylephrine, mean arterial pressure, vascular reactivity to phenylephrine, biochemical markers of organ damage, survival and aorta protein nitrosylation profile. Sepsis substantially decreases blood pressure and the response of aorta rings and of blood pressure to phenylephrine, as well as increased plasma levels of organ damage markers, mortality of 60% and S-nitrosylation of aorta proteins increased during sepsis. Treatment with DTNB 12h after septic shock induction reversed the loss of response of aorta rings and blood pressure to vasoconstrictors, reduced organ damage and protein nitrosylation and increased survival to 80%. Increases in protein S-nitrosylation are related to cardiovascular dysfunction and multiple organ injury during sepsis. Treatment of rats with DTNB reduced the excessive protein S-nitrosylation, including that in calcium-dependent potassium channels (BKCa), reversed the cardiovascular dysfunction, improved markers of organ dysfunction and glycemic profile and substantially reduced mortality. Since all these beneficial consequences were attained even if DTNB was administered after septic shock onset, protein (de)nitrosylation may be a suitable target for sepsis treatment.

Hidrogel oftálmico de cisteamina para el tratamiento de la cistinosis ocular / Cysteamine ophthalmic hydrogel for the treatment of ocular cystinosis

La cistinosis ocular es una enfermedad rara que se caracteriza por el depósito de cristales de cistina a nivel corneal, los cuales dificultan la visión de los pacientes. La cisteamina oral se administra en forma de cisteamina, pero esta no alcanza la córnea debido a la falta de vascularización corneal, por lo que es necesaria la aplicación tópica ocular. El objetivo del presente trabajo es determinar la estabilidad de un hidrogel oftálmico de cisteamina, potencialmente formulable en servicios de farmacia hospitalaria, conservado este bajo diferentes condiciones de almacenamiento durante un periodo de 30 días. Los parámetros físicos y químicos evaluados han sido la osmolalidad, el pH y la concentración de cisteamina, siendo esta última valorada mediante un método de cromatografía líquida de ultra alta presión, empleando un detector de masas en tándem (UPLC-MS/MS). Los ensayos descriptivos se han basado en la medición de la transparencia y los ensayos microbiológicos en la realización de pruebas de esterilidad. Los resultados obtenidos permiten concluir que el hidrogel de cisteamina es estable durante un periodo de 30 días, recomendándose que su conservación sea en nevera (AU)

Ocular cystinosis is a rare disease characterised by the deposit of cystine crystals on the corneal surface, which hinder patients' eyesight. Oral cysteamine is given as cysteamine; however, it does not reach the cornea due to the lack of corneal vascularization making necessary its administration by the topical ocular route. The aim of the present study is to determine the stability of an ophthalmic hydrogel of cysteamine, which can be potentially prepared at hospital pharmacy departments, under different preservation conditions during a follow-up of 30 days. Different physical and chemical parameters were evaluated: osmolality, pH and cysteamine concentration, which has been measured by a method of ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). Descriptive assays were also performed, such as transparency measurement and microbiological assays in order to verify its sterility. The obtained results allow us to conclude that the cysteamine hydrogel is stable during 30 days, being recommendable its preservation in refrigerated conditions (AU)